Research goal

To improve the prediction of likely disease outcomes in people with multiple sclerosis (and other neuroimmunological diseases), to ultimately inform patient management strategies and treatment individualisation.

Research overview

Multiple Sclerosis (MS) is an autoimmune degenerative disease of the central nervous system. Globally MS affect about 2.5 million people, in Australia, MS prevalence is around 1 in 1,000, equating to about 25,000 Australians. Multiple Sclerosis represents a significant burden to Australian society with an estimated annual cost of $1 billion AUD, due the cost of lost productivity, disease-modifying therapy, and other healthcare-associated costs that increase markedly with disease-associated disability.

The long-term disability outcomes of people with Multiple Sclerosis (MS) vary greatly, ranging from little or no disease-associated disability, to severe disease that can render individuals wheelchair or bed-bound within a decade of onset. Further, MS disproportionately affects 2.5 times more women than men, and is usually diagnosed during a woman’s reproductive years (20-40).

Our research falls under three broad umbrellas:

Identification of genetic and epigenetic signals associated with disease outcomes and disease states

Interrogation of the effects of pregnancy and hormones on disease outcomes in neuroinflammatory conditions

Our research integrates biological data with clinical outcomes data with the aim of better understanding what drives disability outcomes in MS, and similar neuroimmunological conditions such as neuromyelitis optica spectrum disorder (NMOSD).

Projects

We collaborate widely on many of our projects, and have strong links with the MSBase Registry, headed by Prof Helmut Butzkueven. We have a number of on-going projects that utilize genetic, genomic, biostatistic, and epidemiological methodologies to approach our research aims. Some of our current projects are listed below.

Multiple sclerosis, an autoimmune, neurodegenerative condition, is the most common cause of non-traumatic neurological disability in young adults. At present twelve immunomodulatory or immunosuppressive therapies with varying levels of treatment efficacy are approved for the treatment of MS in Australia (13 globally). All drugs have been shown to reduce relapse rates in clinical trials, and some have also been shown to have disability progression and MRI benefits. However, individuals are known to have variable responses to these therapies, and can be classed as treatment responders, intermediate responders and non-responders. This project aims to identify genetic markers of treatment response to ultimately allow the stratification of patients for therapeutic choice, reduce treatment trial-and-error and prolong patient quality of life.

This project aims to determine what impact pregnancy has on the long-term outcomes of women with multiple sclerosis. At present, it is believed that pregnancy is either beneficial, or has no effect on the outcomes of women with MS. However, our understanding of the effects of pregnancy is confounded, as it could be that women with milder MS are more likely to have pregnancies than women with more severe MS. Here we are using sophisticated biostatistical approaches to assess the effects of pregnancy on MS outcomes, and overcome some of the biases in the literature reported to-date.Collaborators: St Josef Hospital, Bochum, Germany; Charles University, Prague; John Hunter Hospital, Newcastle, NSW; Amiri Hospital, Kuwait City, Kuwait; Royal Melbourne Hospital, VIC; University of Melbourne, VIC; Eastern Health; VIC. MSBase Registry members.

Project description: Relapse-onset MS is characterised by periods of neurological symptom exacerbation (relapses), and periods of neurological stability (remission). Relapses have been shown to associate with accumulating neurological disability. It has been demonstrated that relapse rates diminish during pregnancy in women with relapse-onset MS, being lowest in the third trimester, but then tend rebound post-partum. However, not all women experience post-partum relapses. The determinants of post-partum relapse timing and severity remain poorly understood. Identification and characterisation of the determinants of post-partum relapse will allow for better stratification of patients at risk of post-partum relapse and will better inform the clinical management of these patients.Collaborators: MSBase Registry

The risk of persistent Human Papillomavirus (HPV) infection, cervical dysplasia and HPV-related cancers is unknown in women with multiple sclerosis (MS). Given the long-term and serial exposure of patients to immunomodulatory and immunosuppressive treatments, it is important to determine additional modifiable risk factors for cervical dysplasia in the MS population compared to other women. Understanding cervical dysplasia and cancer risk factors in women with RRMS, as well as HPV vaccination rates, will help guide the development of strategies that may help reduce risk of this serious adverse outcome in women with MS. Collaborators: A. Prof Julia Brotherton, Victorian Cervical Screening Registry; Prof. Helmut Butzkueven, MSBase Registry